Preliminary topline results from Phase 2b ALTISSIMO trial unveiled

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Graybug Vision’s Phase 2b ALTISSIMO trial of GB-102 focuses on the treatment of wet age-related macular degeneration.

Graybug Vision Inc. has provided preliminary topline data from the 12-month treatment phase of its Phase 2b ALTISSIMO trial of GB-102 for the treatment of wet age-related macular degeneration (wet AMD), Graybug’s microparticle depot formulation of sunitinib malate injected intravitreally.

According to the company, the ALTISSIMO trial is a masked and controlled Phase 2b dose-ranging study of two doses of GB-102 with a single control arm of patients on aflibercept, conducted across 33 study sites in the United States.

The GB-102 phase 2b ALTISSIMO core trial centered around GB-102, a proprietary microparticle depot formulation of the pan-vascular endothelial growth factor (pan-VEGF) inhibitor, sunitinib malate, developed to be administrated intravitreally twice a year, according to a company news release.

GB-102 aims to reduce the need for frequent intravitreal injections by extending the length of treatment to six months or longer.

The primary endpoint is median time to first supportive therapy with a vascular endothelial growth factor (VEGF) inhibitor, and secondary endpoints are pharmacodynamics measures of mean change of best-corrected visual acuity (BCVA) from baseline and mean change of central subfield thickness (CST) of the retina from baseline.

The company noted that the trial was originally designed to evaluate two separate doses of GB-102, 1mg and 2mg, injected every 6 months as compared with aflibercept injected every 2 months. Based on the results of an interim safety analysis, the 2mg dose was discontinued after the initial dose, and all patients in that arm were switched to 1mg for their second dose.

According to the company, analysis of the ALTISSIMO 1mg arm shows the primary endpoint of median time to first supportive therapy was 5 months. Furthermore, 48% of patients did not require supportive therapy for at least 6 months, and 62% of patients for at least 4 months or more, at least once during the trial. Overall, the 1mg dose performed better than the 2mg dose.

Overall, GB-102 1mg was well-tolerated. There were no drug-related serious adverse events, and the majority of drug-related adverse events were mild to moderate.

Medication was detected in the anterior chamber in less than 10% of GB-102 1mg injections, and no adverse event required surgical intervention. There was no vision-threatening inflammation observed, and there was no increase in intraocular pressure reported.

CST and BCVA were measured as secondary endpoints. CST in the GB-102 1mg arm was consistent with the study control arm. The mean change from baseline for BCVA for all 20 completers was approximately 9 letters lower across all time points, on average, than that observed in the study control arm.

Following the treatment phase, patients were surveyed as to their satisfaction with their treatment compared to their treatment prior to entering the trial.

Over 80% of responding patients who had been treated with GB-102 reported that they were equally or more satisfied with their treatment, similar to the satisfaction expressed by patients treated with aflibercept.

According to the company, ALTISSIMO will continue through a 6-month extension in which 28 of the 50 patients who completed their Month 12 visit were eligible and agreed to continue masked clinical monitoring.

Patients will continue with monthly visits until the point at which they require additional supportive therapy, up to a maximum of 6 months.

As of today, 22 patients have successfully completed 2 months or more of this six-month extension period without the need for further treatment.

Parisa Zamiri, MD, PhD, chief medical officer of Graybug, said the company will determine its next steps after completing the full analysis of the ALTISSIMO results, which is anticipated to occur in the second quarter.

“We are very grateful to all patients, investigators and staff who participated in the ALTISSIMO trial, and look forward to the read-out of the extension trial data,” Zamiri said.